The overall objective of this proposal is to carry ot a systematic investigation of the factors which affect lead pharmacokinetics in experimental animals. Parameters which alter lead absorption, distribution and elimination will be studied as potential avenues for lead poisoning prevention and treatment Inhibition of lead absorption is studied focusing on the processes which govern lead absorption in immature animals. These processes are (a) dissolution, (b) transit and (c) permeability of lad from paint chips in the gastrointestinal tract. Interferences of each of these processes can potentially alter the absorption characteristics of lead. Dissolution of lead from paint chips can be inhibited by precipitating anions, antacids and ion-exchange resins. Transit of lead can be promote by metoclopramide and slowed by buffered carbohydrate solutions. Permeability of lead across the gastrointestinal barrier can be affected by the presence of competing metal ions. These approaches will be tested in the proposed research, using both in vitro and in vivo models. The intrinsic factors governing lead clearance from blood and lead entry into brain are not well defined in the literature. The fraction of "free" (diffusable) lead in the plasma may play a central role in these processes. Distributive changes among components of blood may give rise to concomitant changes in brain lead levels. In this proposal, the erythrocyte and plasma protein binding characteristics in different animal species are compared. The inter-relationship between erythrocyte lead bining, plasma "free" lead, brain lead and lead clearance from the boy will be examined. The effect of metal ions such as calcium, zinc and magnesium on brain lead entry and egress will be investigated.